Osteogenesis Imperfecta

What is osteogenesis imperfecta?

• brittle bone disease

• disorder of collagen synthesis leads to recurrent fractures and deformation

Causes of osteogenesis imperfecta

• most inherit from parent (autosomal dominant inheritance)

• 25% of cases caused by genetic mutation occurring spontaneously

Osteogenesis imperfecta pathophysiology

• due to defect in collagen synthesis

• more than 150 mutations identified (all affecting genes that code for type 1 collagen)

  • type 1 collagen: major structural component in ECM of bone, skin and tendons

• mutated genes instruct body to make too little type 1 collagen or abnormal polypeptide chains that cannot form the triple helix of type 1 collagen

Type 1 osteogenesis imperfecta collagen production

reduced by 50%

Type 2 osteogenesis imperfecta collagen production

reduced by 80%

Diagnostic tools for osteogenesis imperfecta

• DNA testing

• prenatal ultrasound

• fetal 3D CT scan

• human chorionic villus biopsy

• DEXA: low bone mineral density

• x-ray films

Type 1 osteogenesis imperfecta

• most common

• mildest clinically

• two types

  • A: teeth are normal

  • B: dentinogenesis imperfecta is a feature (abnormal tooth development)

• grayish-blue sclerae at birth

• mild to mod bone fragility

• osteopenia

• mild femoral bowing at birth

• generalized ligamentous laxity with joint hypermobility

• 50% develop hearing loss by teens

Type 2 osteogenesis imperfecta

• most severe form

• lethal: mainly due to pulmonary complications from rib and vertebral fractures

• severe bone fragility

• at birth, short limbs, small chests, and soft skulls

• sclerae dark blue or gray

• intrauterine fractures common

• respiratory and swallowing problems

Type 3 osteogenesis imperfecta

• severe form

• usually result of new mutations

• fractures and deformities from utero

• large skull (upper portion), triangular face

• dentinogenesis imperfecta

• blue to pale blue sclerae

• healing is impaired

• severe osteopenia

• severe disorganization of growth plate structure

• progressive kyphoscoloiosis

• early onset hearing loss

• very short stature

• lifespan may be shortened due to respiratory conditions

Type 4 osteogenesis imperfecta

• moderate form

• diagnosis can be made at birth but often occurs later

• normal birth weight and length

• two subsets

  • A: normal dentition

  • B: dentinogenesis imperfecta (majority)

• slightly gray sclerae

• moderate bone fragility

• mild femoral bowing at birth

• osteopenia occurs with aging

• scoliosis

• mild bone angulation

• child might not fracture until walking

Osteogenesis imperfecta prognosis

• Types I and IV: milder course, normal lifespan

• Type II: most severe, 90% die in first few weeks

• Type III: mortality related to cardiorespiratory failure stemming from kyphoscoliotic deformity

  • significant risk also exists of basilar invagination of the skull and intracranial bleeding

Osteogenesis imperfecta clinical features

• brittle bones

• joint hypermobility

• thin skin

• weak muscles

• diffuse osteoporosis

• shortened stature

• multiple recurrent fractures

• blue sclerae

• deformed teeth

• deafness

• hernias

• easy bruising

• excessive sweating

• scoliosis

• pectus deformity

osteogenesis imperfecta metabolic defects

• elevated serum pyrophosphate

• decreased platelet aggregation

osteogenesis imperfecta cardiovascular complications

• aortic and mitral valve insufficiency

• aortic dissection

Reasons for delayed development of motor skills in osteogenesis imperfecta

• poorly developed muscles

• hypermobility of joints

• multiple fxs requiring immobilization

osteogenesis imperfecta medical management

• no cure

• manage fractures

• promote function and independence

osteogenesis imperfecta fractures

• most heal well

• short-term immobilization

• prevention important

• treatment options

  • surgery

  • medications

  • healthy lifestyle

  • PT

osteogenesis imperfecta medications

• biphosphonate drugs: slows loss of bone, does not build new bone

• growth hormones

• stem cell therapies

• anti-sclerostin antibody

• current antibody studies

osteogenesis imperfecta healthy lifestyle

• adequate intake of calcium (maintain bone density), vitamin C (promote healing)

  • large doses not recommended

• avoid smoking, alcohol, caffeine, steroid medications

  • can affect bone density

• genetic counseling

Role of PT in osteogenesis imperfecta

• protective handling and positioning

• strengthening

• adaptive equipment

• ambulation

• post-surgery

• aquatics

• education/prevention

Type 1 osteogenesis imperfecta ambulation

• majority of children ambulate either as functional or household ambulators

• 50% walk without any type of AD as community ambulators

Type 3 osteogenesis imperfecta ambulation

½ are dependent on power mobility, with only 27% becoming household ambulators

Type 4 osteogenesis imperfecta ambulation

26% are community ambulators and 57% are household ambulators

What are the best predictors of ambulatory status?

• disease type

• ability to sit by 9 or 10 months of age

Role of PT in osteogenesis imperfecta

• always be aware of the infant’s limbs

• in severely affected babies

  • used a covered pillow for transporting baby

• allow infant to explore independent movement

• support infants in many positions

  • allows muscles to develop to aide in sitting and standing down the road

• educate

osteogenesis imperfecta education

• teach the family how to care and handle their newly diagnosed baby

• promote independent function: teach family and patient how to modify home and school environment to accommodate their short stature and low strength

• local support groups

osteogenesis imperfecta precautions

Do not…

• push or pull on a limb

• lift an infant from under the armpits

• lift an infant by the ankles

• perform activities that will jar or twist the spine